Conformational flexibility of voltage gated dihydropyridine sensitive calcium channel in hydrated DMPC bilayer

We have built a model for Ca2+ channel using amino acid sequence from S3 helix of the fourth internal repeat of alpha 1 subunit of dihydropyridine sensitive calcium channel from rabbit skeletal muscle, on the basis of X-ray crystallographic data on four helix bundle. The assembling of the geometry of the pore was achieved using a sixteen residues peptide fragment from short SSI/II loop (residues 1010-1025) which had F1013 and E1014 residues, considered to be important for the drug induced activity of the channel. This had hairpin bend between F1013 to W1016. The drug 2,6-dimethyl 3,5-dicarbomethoxy-4 (2-nitrobenzyl) 1,4 dihydropyridine (DHP) (nifedipine), which is a calcium channel inhibitor used in the treatment of cardiovascular diseases, was introduced, interacting with these two residues via Ca2+ ion. Two more Ca2+ ions were introduced in the pore. The model was incorporated in the bilayer of 36 dimyristoyl phosphatidyl choline (DMPC) molecules with 1201 water molecules and simulated for 200 picoseconds (ps) after equilibration for 120 ps. We also simulated the channel model in vacuum and in aqueous environment for comparison. The latter was unstable after 120 ps. The geometric parameters of the pore are analysed by MOLMOL, PCURVE 3.1 and a special program ANHELIX developed by us. Stability of the pore dimensions during simulations is discussed in this paper.